Page 170 - Read Online

Neuroimmunol Neuroinflammation 2019;6:15 I http://dx.doi.org/10.20517/2347-8659.2019.019 Page 9 of 24

type 5XFAD mice. st3gal5-deficient 5XFAD mice also performed significantly better in a cognitive test
than the wild-type 5XFAD control group. Finally, the treatment of wild-type 5XFAD mice with the sialic
acid-specific Limax flavus lectin resulted in substantial improvement of AD pathology. Thus, our study
establishes an important role for major brain glycolipids in the regulation of neuroinflammation, neuronal
plasticity, synaptic functions, and cognitive ability after a neuronal injury during TBI- and AD-related
neurodegeneration.

12. Analysis of the association of MIR124-1 and its target gene RSG4 polymorphisms with
major depressive disorder and antidepressant response

Duan Zeng, Shen He, Shun-Ying Yu, Guan-Jun Li, Chang-Lin Ma,Yi Wen, Yi-Feng Shen, Yi-Min
Yu, Hua-Fang Li

Department of Psychiatry, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine,
Shanghai, China

Increasing evidence has indicated that dysfunction of miR-124 and target gene regulator of G protein
signaling 4 (RGS4) may be involved in the etiology and treatment of major depressive disorder (MDD).
However, the molecular mechanisms are not fully understood. This study aimed to investigate whether
common genetic variations in these two genes are associated with MDD and therapeutic response to
antidepressants in the Chinese population. Three polymorphisms including rs531564 [a functional single-
nucleotide polymorphism (SNP) in MIR124-1], rs10759 (a microRNA-binding site SNP in RGS4), and
rs951436 (a promoter SNP in RGS4) were genotyped in 225 Chinese MDD patients and 436 controls.
Among the MDD patients, 147 accepted antidepressant treatment for eight weeks with therapeutic
evaluation at baseline, Week 2, Week 4, Week 6, and Week 8 using the 17-item Hamilton Rating Scale for
Depression. Multifactor dimensionality reduction (MDR) was used to identify gene-gene interactions. No
significant association with MDD was discovered in single-SNP analyses. However, in the optimal model
containing rs531564, rs10759, and rs951436 SNPs by MDR analysis, the P-value was 0.0024, the accuracy of
the sample test was 0.49, and the cross-validation consistency was 10/10. Values of ORs and 95% confidence
interval (CI) indicated that the combined action could increase the risk of MDD (OR = 1.67, 95%CI: 1.20-
2.33). In pharmacogenetic study, a significant association was found in genotypic frequencies of rs951436
2
between the responder and non-responder groups (x = 6.191, P = 0.045, correction P = 0.135) as well as
2
between the remitter and non-remitter groups (x = 7.216, P = 0.026, correction P = 0.078). For further
analysis, the rs951436 heterozygote carriers had threefold probabilities of achieving clinical complete
remission (OR = 3.00, 95%CI: 1.33-6.76, P = 0.007, correction P = 0.021) and 3.21-fold probabilities of
achieving clinical response (OR = 3.21, 95%CI: 1.13-9.14, P = 0.022, correction P = 0.066) as compared with
rs951436 homozygotes (AA + CC) after eight-week treatment. Moreover, the homozygous (AA + CC) of
rs951436 showed a worse response to antidepressant treatment and had lower percent reduction of HAM-D
scores over eight weeks than heterozygous AC, and significant associations were found at Week 6 (AA +
CC vs. AC: 53.58 ± 27.04 vs. 61.34 ± 21.54, t = -2.08, P = 0.040) and Week 8 (AA + CC vs. AC: 60.17 ± 29.56
vs. 70.19 ± 20.41, t = -2.404, P = 0.018) after the adjusting for age and gender. In conclusion, an interaction
effect of MIR124-1 and RGS4 polymorphisms may play a more important role than individual factors for
MDD development. Moreover, RGS4 gene polymorphisms may be associated with antidepressant response
among the Han population such as Weighted Correlation Network Analysis to explore pathogenic genes
related to MDD, schizophrenia, and other psychiatric disorders. All directions of her research program are
supported by the China National Major Project.